Molecular Dynamics Simulations of Supramolecular Anticancer Nanotubes

We report here on long-time all-atomistic molecular dynamics simulations of functional supramolecular nanotubes composed by the self-assembly of peptide-drug amphiphiles (DAs). These DAs have been shown to possess an inherently high drug loading of the hydrophobic anticancer drug camptothecin. We probe the self-assembly mechanism from random with ∼0.4 μs molecular dynamics simulations. Furthermore, we also computationally characterize the interfacial structure, directionality of π–π stacking, and water dynamics within several peptide-drug nanotubes with diameters consistent with the reported experimental nanotube diameter. Insight gained should inform the future design of these novel anticancer drug delivery systems

Effect of Nucleotide State on the Protofilament Conformation of Tubulin Octamers

At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) simulations and normal-mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed of two neighboring protofilaments (PFs). We utilize recently reported high-resolution structures of dynamic MTs to simulate a GDP octamer both with and without a single GTP cap layer. We perform multiple replicas of long-time atomistic MD simulations (3 replicas, 0.3 μs for each replica, 0.9 μs for each octamer system, and 1.8 μs total) of both octamers. We observe that a single GTP cap layer induces structural differences in neighboring PFs, finding that one PF possesses a gradual curvature, compared to the second PF which possesses a kinked conformation. This results in either curling or splaying between these PFs. We suggest that this is due to asymmetric strengths of longitudinal contacts between the two PFs. Furthermore, using NMA, we calculate mechanical properties of these octamer systems and find that octamer system with a single GTP cap layer possesses a lower flexural rigidity

Association of socio-behavioral and physical characteristics with AGM status (Reference: Never diabetic) during the study (based on current fasting plasma glucose and past diagnosis of diabetes) among the participants (N = 269).

<p>Association of socio-behavioral and physical characteristics with AGM status (Reference: Never diabetic) during the study (based on current fasting plasma glucose and past diagnosis of diabetes) among the participants (N = 269).</p

Socio-behavioral and physical correlates and their association with abnormal fasting plasma glucose level, glycemic control and AGM among the participants (N = 269).

<p>Socio-behavioral and physical correlates and their association with abnormal fasting plasma glucose level, glycemic control and AGM among the participants (N = 269).</p

Distribution of socio-behavioral and physical characteristics, fasting plasma glucose (FPG), glycemic control, diabetes/AGM and hypertension among 269 randomly selected subjects in an urban population of India.

<p>Distribution of socio-behavioral and physical characteristics, fasting plasma glucose (FPG), glycemic control, diabetes/AGM and hypertension among 269 randomly selected subjects in an urban population of India.</p